Neonatal thyroid deficiency has differential effects on cell specific markers for astrocytes and oligodendrocytes in the rat brain

Abstract

The effects of thyroid deficiency on the activity of glutamine synthetase (GS) and the number of glial fibrillary acidic (GFA) protein containing cells (the markers for astroglial cells) and on the 2′, 3′-cyclic nucleotide 3′-phosphohydrolase (CNPase) activity (the marker for oligodendroglial cells) were studied in the cerebral cortex, hippocampus and cerebellum of the rat at ages 5, 10, 15 and 25 days, and at day 130 following 102 days of rehabilitation. In the cerebral cortex and hippocampus of control rats, the activity of GS was relatively greater at 5 days and during development it increased earlier than in the cerebellum. The reverse was true for CNPase activity, which during maturation increased earlier in the cerebellum than in the cerebral cortex and hippocampus. Neonatal thyroid deficiency resulted in exactly opposite effects on the marker enzymes for astroglial and oligodendroglial cells: the developmental patterns of GS activity were transiently advanced, while those of CNPase were markedly retarded in all three brain regions. In agreement with the biochemical findings on GS activity, the morphological observations also showed a marked increase in the density of cells containing GFA protein in the different brain regions of 15 day old hypothyroid rats. In the cerebral cortex and hippocampus, in spite of continued thyroid hormone deficiency, the rise in GS activity was restored to normal by 25 days, whereas in the cerebellum the elevation of enzyme activity was restored to normal only after rehabilitation. On the other hand, the effect of neonatal thyroid deficiency on the CNPase activity was more severe in the cerebral cortex and hippocampus than in the cerebellum. In this brain part, the decrease in CNPase activity was restored to normal after a long period of hormonal rehabilitation, but, in comparison with controls, it remained persistently reduced in the cerebral cortex and hippocampus. The present observations, together with our previous findings, would indicate that the effect of thyroid hormone on the maturation of neural cells is cell-type specific. Furthermore, it is proposed that, consistent with the suggestion that astrocytes promote differentiation of nerve cells, the observed hyperplasia and hypertrophy of astrocytes may represent a compensatory response to the marked retardation in neuronal maturation in the hypothyroid rats.